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Should Caffeine Abuse, Dependence, or Withdrawal Be Added to DSM-IV and ICD-10? I I I I I I I I I I I I I I John R. Hughes, M.D., Alison H. Oliveto, Ph.D., John E. Helzer, M.D., Stephen T. Higgins, Ph.D., and Warren K. Bickel, Ph.D. h' tive: The authors reviewed basic science and clinical data on caffeine abuse, depend- ence, and withdrawal in order to make a conclusion about whether these disorders exist and should be included in DSM-IV and ICD-10. Method: Studies were located through comput- erized searches, reference sections of published articles, and written requests. ult : The studies show that abstinence from ca ffeine induces a withdrawal syndrome o f headache, fa- tigue, and drowsiness which begins within 12-24 hours and lasts about 1 week. The syndrome can be severe and appears to be one reason for continued use of coffee. The prevalence of this caffeine withdrawal syndrome is unknown. Use of caffeine may aggravate some common behavioral and medical disorders. In double-blind tests, a subset of coffee and soda drinkers reliably sel f-administered ca f feinated beverages in pre ference to unca f feinated beverages. Clinical indicators o f dependence, such as di fficulty stopping use o f ca f feine and use despite harm, have not been documented. Conclusions: Caffeine withdrawal but not caffeine abuse or dependence should be included as a diagnosis in DSM-N and ICD-10. Future research should focus on whether some ca ffeine users exhibit clinical indicators o f drug dependence. (Am J Psychiatry 1992; 149:33-40) C affeine is the most widely used drug in the world. For example, over 85% of Americans ingest caf- feine daily, and the average caffeine intake is approxi- mately 200 mg/day (1, 2). Excessive caffeine intake is especially prevalent among psychiatric patients (3-5); 22% of psychiatric inpatients use more than 750 mg/day (5), compared to 9% of the general population (2). Caffeine can be ingested from brewed coffee (100 mg/6 oz), instant coffee (65 mg/6 oz), tea (40 mg/6 oz), soda (50 mg/12 oz), and over-the-counter analgesics, antihistamines, stimulants, and weight-loss aids (S0- 200 mg/tablet). Whether caffeine is a drug of abuse or dependence and whether cessation of caffeine use can induce withdrawal symptoms have been examined in previous reviews (6-8); however, none of these has dis- Presented at the annual meeting of the American Psychological As- sociarion, Boston, Aug. 13, 1990. Received Oct. 23, 1990; revision received April 18, 1991; accepted April 29, 1991. From the Human Behavioral Pharmacology Laboratory, Departments of Psychiatry, Psychology, and Family Pracrice, University of Vermont. Address re- print requests to Dr. Hughes, Human Behavioral Pharmacology Laboratory, Department of Psychiatry, University of Vermont, 38 Fletcher Place-Ira Allen School, Burlington, VT 05401. Supported by grants DA-04843, DA-06626, DA-05382, and DA- 06205, Research Scientist Development Award DA-00109 (to Dr. Hughes), and First Independent Research Scientist in Transition Award DA-04545 (to Dr. Higgins) from the National Institute on Drug Abuse. Copyright ® 1992 American Psychiatric Association. cussed caffeine use disorders in the light of DSM or ICD criteria. Many definitions of and criteria for drug abuse, de- pendence, and withdrawal have been proposed. To in- crease the comprehensiveness of this review, broad definitions of these terms are used. "Withdrawal" re- fers to time-limited effects due to cessation (9). Drug tolerance is usuallv associated with withdrawal (10). "Abuse" refers to harmful or hazardous use (ICD-10, DSM-rII-R) or use for socially disapproved reasons (10). "Dependence" refers to a constellation of symp- toms outlined by Edwards and colleagues (11, 12), ICD-10, and DSM -111-R that includes withdrawal, tol- erance, and abuse. "Dependence" in these schemas also focuses on loss of control over drug use, excess time in procuring or preparing the drug, progressive neglec*t of self because of drug use, narrowing of the pattern of drug use, and rapid reinstatement of drug dependence upon relapse. ~ FP CAFFEINE W=RAWAL O.7 Basic Science Criteria C~D The DSM-111-R definition of withdrawal is "develop- ~ ment of a substance-specific syndrome that follows the ~ cessation of, or reduction in, intake of a psychoactive sub- ~ stance that the person previously used regularly" (p. 118). Am J Psychiatry 149:1, January 1992 33

I I I I I I I I I I I I I I I I I CAFFEINE DISORDERS AND DSM-Il' Other criteria include demonstration of relief of the syndrome bv the readministration of the drug. rebound or "overshoot" effects, and physical changes (9). Experimental induction of withdrawal symptoms. Six studies have examined caffeine deprivation in non- human subiects chronically treated with caffeine (13, 14). Most found that deprivation of caffeine decreased locomotor activity or disrupted performance to below baseline levels (13, 14). We are unaware of studies of changes in physiological, hormonal, or biochemical processes in nonhuman subjects. In over 14 experimental trials with human beings, headache, decreased arousal, and fatigue consistently occurred upon cessation of caffeine use (14). These symptoms occurred during well-controlled, blind dep- rivation of caffeine alone (e.g., substitution of decaf- feinated coffee) and were reversed by readministration of caffeine. Several other withdrawal symptoms have been reported, including anxiety, nausea, and craving for caffeine, but these have not been as well docu- mented (14). Caffeine withdrawal symptoms begin 12- 24 hours after deprivation, peak at 20-48 hours, and last about 1 week-(14). One study (15) showed that in some coffee drinkers, withdrawal symptoms reliably occurred with repeated substitutions of decaffeinated coffee (i.e., on five or six of six tests). Cessation of caffeine also has biochemical and physi- ological effects, such as increased blood pressure (16), 3-methoxy-4-hydroxyphenylglycol (MHPG) (17), and heart rare orientation response (18) and decreased (3- adrenoreceptor sensitivitv (19). Other studies have failed to find effects of caffeine deprivation on bio- chemical and physiological measures such as blood pressure (20), levels of carecholamines (20), heart rare (20),/and muscle tension (21). Several studies (18, 22-24) have shown decreases in performance on vigilance and psychomotor tasks after subjects stopped using caffeine. In addition, in most of the studies which have shown that acute doses of caf- feine can improve performance, subjects have been de- prived of caffeine for 12 hours. Thus, these studies may have been demonstrating reversal of withdrawal effects rather than direct effects of caffeine (25). Factors predisposing to withdrawal symptoms have not been well studied. Two experimental studies (26, 27) reported that the severity or probability of with- drawal effects is related to the maintenance dose of caf- feine, but other studies (15, 24) did not find this. In two studies (27, 28), withdrawal symptoms occurred at doses of caffeine as low as 100 mg/day. One case report (29) suggested that neonatal with- drawal symptoms could occur after heavy maternal caf- feine intake; however, empirical studies are lacking. In addition, neonatal withdrawal symptoms have not been found with maternal use of other stimulants (e.g., cocaine, amphetamine, and nicotine). Several mechanisms could account for the symptoms of caffeine withdrawal: greater sensitivity to endoge- nous adenosine (caffeine is an adenosine antagonist) (30), changes in adrenergic sensitivity (19), or, in the 34 case of ::eadaches, increased cerebral blood flow (31). Airhouai: there are some data supporting these mecha- nisms. the data are not yet convincing. Toler.:r.ce. Tolerance is usually associated with with- drawal. T olerance is defined in DSM-III-R as the "need for marl:ediy increased amounts of the substance (i.e., at leas: a 50°o increase) in order to achieve intoxication or desisec: effect, or markedly diminished effect with conrinuec use of the same amount" (p. 168). The work- ing drai" or ICD-10 has a similar definition. Several s:-udies (32-34) have documented tolerance to the effe ,: of caffeine in nonhuman subjects. In addi- tion, repeated dosing of caffeine in nonhuman subjects increases the number and sensitivity of brain adenosine receptors. which might be a mechanism for the devel- opment of tolerance (35, 36). In hurnans, experimental administration of caffeine induces tolerance to hemodynamic and other physi- ological e--::ects of caffeine (20). An experimental dem- onstration o: tolerance to the behavioral effects of caf- feine in hum.ans has not been reported. Previous studies have indicated that caffeine has fewer negative subjec- tive effect_ in persons who drink large amounts of cof- fee than in those who drink small amounts (37-40); however. «•aether this is due to acquired tolerance or to self-sele-tion by individuals differing a priori in sensi- tivity to ca~ieine is unclear. Finally, studies linking the degree of czffeine tolerance and that of caffeine with- drawal symoroms have not been reported. Clinical Cr::eria Severit-v o= w•ithdrawal symptoms. DSM-III-R states that caf7ei.ne «•ithdrawal was not included because "al- though the existence of a caffeine withdrawal headache is well estabiished, the syndrome is usually not severe enough to warrant clinical attention" (p. 138). How- ever, several double-blind, placebo-substitution trials have documented the occurrence of caffeine with- drawal headache, drowsiness, or fatigue that interfered with norma: funcrfion and was at times incapacitating. In the firs: report (41), 22 men were given 600-750 mg/day of cafieine for 6-7 days, and then placebo was substituted. On 21 (55%) of 38 trials, headache "as se- vere as the subject had ever had" was reported. In six (27%) of the subjects, the headache was consistently accompanied by some degree of nausea, and vomiting occurred in ttivo !9%0) of the subjects. In four more-recent studies, decaffeinated coffee was substituted for caffeinated coffee in a double- blind manner. In the first study of six heavy coffee drinkers (2 2'. on six (10%) of the 63 tests the head- ache was rated as strong. In a second study of moder- ate coffee drinkers (24), severe headaches were re- ported on eight (15%) of 55 trials, severe drowsiness on nine (16°0) of the trials, and severe fatigue on six (11%) of the trials. In a thi-rd study (15), two of 10 subjects dropped out because they had headaches on decaffeinated-ti:offee days that were severe enough to prohibit producrive work at the subjects' jobs. In a Am J Psychiatn, 149:1. Ianuarv 199'

I I I I I I I I I I I I I I I I fourth study of subjects taking 100 mg/dav of caffeine in capsules (42), headache and fatigue occurred even upon deprivation of this low dose. In fact, "the head- ache, lethargy and nausea experienced after placebo substitution in six of the seven subjects were incom- patible with normal functioning; subjects occasionally reported going to bed early with flu-like symptoms and two subjects reported vomiting. We judge the peak level of disruption encountered by six of the seven subjects to be clinically significant" (27). Prevalence of withdrawal symptoms. Among retro- spective surveys, an early study (43) found that 8%-9% of 239 housewives who drank coffee reported headaches after cessation, and 38 % stated that they would feel "half- awake" if they stopped coffee use. Among headache pa- tients, 20% stated that lack of coffee would result in head- aches (41). Among psychiatric inpatients, 20% reported headaches upon caffeine cessation (44). Such survey data may actually underestimate the prevalence of withdrawal symptoms, as many caffeine users may be unaware that intermittent drowsiness, headaches, and fatigue could be due to the absence of caffeine. Among prospective studies, a study of postoperative headache found that the prevalence of headaches in- creased from 0% in nonusers of caffeine to 43%-46% in those who used 200-1,000 mg/day to 73% among those who used more than 1,000 mg/day (26). In three trials, among nonpatient (i.e., volunteer) moderate cof- fee drinkers (3-7 cups/day), the prospective prevalence of headaches was 23%-56%; of drowsiness, 38%; and of fatigue, 38% (15, 24, 45). The prospective preva- lence of caffeine withdrawal headaches following cessa- tion of heavy caffeine-use (more than 600 mg/day) in patient samples has been reported to be between 82% and 100% (41, 46). Withdrawal symptoms and self-administration o f caffeine. In three studies (15, 22, 24), subjects who had withdrawal headaches, drowsiness, or fatigue upon placebo substitution were subsequently more likely to self-administer caffeinated coffee in preference to decaf- feinated coffee than were subjects who did not experi- ence these withdrawal symptoms. In two studies (15, 24), the occurrence of withdrawal effects was followed by self-administration more than 80% of the time; however, on 30%-40% of occasions, self-administra- tion occurred in the absence of withdrawal symptoms. Thus, the presence of withdrawal symptoms is highly predictive of caffeine self-administration, but the ab- sence of withdrawal symptoms does not predict the ab- sence of caffeine self-administration. Conclusions With Respect to Caffeine Withdrawal -At the present time, there appears to be sufficient evidence to justify inclusion of a caffeine withdrawal syndrome in DSM-IV and ICD-10, with headache, de- creased arousal, and fatigue listed as the valid symp- toms. These symptoms have been shown to be due to the specific deprivation of caffeine, they have a charac- teristic rime-limited course, they can occur at moderate HUGHES, OLI\1TO. HELZER, ET ?,L. caffeine intakes, they can occur in a substantial propor- tion of coffee drinkers, and they appear to contribute to the self-administration of caffeine. Finally, the earlier rationale for not including caffeine withdrawal-i.e., the symptoms are not severe-appears not to be true. Experimental tests of tolerance to the behavioral effects of caffeine and further study of tfle association of toler- ance and withdrawal symproms. the biochemical mechanisms of withdrawal symptoms, and the preva- lence of symptoms of caffeine withdrawal are needed. Inclusion of the Caffeine Withdrawal Syndrome and the Goals o f DSM Clinical usefulness for making treatment and man- agement decisions. Heavy caffeine use appears to be quite prevalent among psychiatric patients (3-5) and alcohol and drug abusers (47, 48;. Many psychiatric, alcohol/drug abuse, and medical inpatient units pro- hibit caffeinated coffee; thus, some patients may be forced into a caffeine withdrawal syndrome when en- tering these units. This could interfere with the diagno- sis and treatment of such patients. since the symptoms of caffeine withdrawal (headache, fatigue, and drowsi- ness) could mimic or falsely exaggerate symptoms of anxiety, depression, dementia, delirium, stimulant withdrawal, or drug-induced sedation. Having a diag- nosis of caffeine withdrawal swdrome would sensitize clinicians to this possibility. Prevalence is a consideration for clinical usefulness. On the basis of the data described earlier, a conserva- tive estimate of the prevalence of caffeine withdrawal symptoms is that 5% of caffeine users develop head- ache, drowsiness, or fatigue upon cessation. Even such a low prevalence is important, given that 85%-90°0 of U.S. adults use caffeine daily. Acceptability to clinicians and researchers. Clinicians and scientists may welcome the inciusion of a caffeine withdrawal syndrome, since other stimulants (e.g., am- phetamine and cocaine) have accepted withdrawal syn- dromes but caffeine does not. Opposition to inclusion of a caffeine withdrawal svndrome might come from those who believe that it is less severe than other with- drawal syndromes. We are unaware of survey or ex- perimental comparisons of caffeine with other with- drawal syndromes. However, the data we have cited suggest that symptoms of ca=feine withdrawal can be severe and can interfere with role functioning. In addi- tion, the data suggest that the presence of caffeine with- drawal symptoms contributes to the continued use of caffeinated beverages. •.Opposition to including a ca=feine withdrawal syn- drome might also be due to a fear that its acceptance implies acceptance of caffeine as a drug of dependence. In recent years, many drugs tnat are not drugs of de- pendence have been identified as producing withdrawal symptoms upon cessation (e.g., antidepressants and an- tipsychotics) (49, 50). Thus, accepting that wjthdrawal of a drug can produce symptoms no longer necC5sarily implies accepting that it is a drug of dependence- I Am J Psychiatry 149:1, January 1992 2046399645 , 35

f I I I I I I I I 1 1 I I I I 1 I CAFFEINE DISORDERS AND DSh1-IV C~FrEL'vE ABUSE Basic Science Criteria The DSM-III-R criteria for psychoactive substance abuse are "continued use ... despite knowledge of hav- ing a persistent or recurrent social, occupatio:aal, psy- chological, or physical problem that is caused or exac- erbated by use of the substance" and "recurrent use of the substance in situations when use is physicaliy haz- ardous (e.g., driving while intoxicated)" (p. 169). A working draft of 1CD-10 defines harmful use as "a pat- tern of use which is causing damage to health. Tne dam- age may be physical or mental." Two basic science ar- eas relevant to abuse are caffeine psychoac~-,-itv and harmful medical effects. Psychoactive e ffects o f ca f feine. Basic science defini- tions of psychoactiviry usually refer to the ability to dis- criminate between a drug and placebo on the basis of the drug's CNS effects. Nonhuman subjects readilv dis- criminate caffeine from placebo and respond as if caf- feine has weak amphetamine-like effects (51-54). Hu- mans also readily discriminate caffeine, even at very low doses (e.g., 10-56 mg) (42, 55). In studies of self-reported effects, single doses (100- 400 mg) of caffeine produce slight increases in elation, positive mood, and amphetamine-like effects ;39, 55- 60). These effem are generally less consistent and of a smaller magnitude than those seen with amphetamine. In addition, at these same doses, caffeine often produces several presumably aversive effects (e.g., increased anxiety and dysphoria) (61, 62). Harm ful e f fects o f ca ffeine. Reviews vary R-idelv in their conclusions about whether caffeine can cause physical disorders (8, 63). However, the DSM-111-R cri- teria for abuse include the ability of a drug not only to initiate a new disorder but also to aggravate an existing disorder. With respect to the latter category. a recent survey (64) indicated that more than 75% of physician specialists recommended cessation of caffeine for pa- tients with several common disorders: anxiety, arrhyth- mias, esophagitis, fibrocystic disease, insomnia, palpi- tations, and tachycardia. $e.havioral disorders resulting from caffeine use are we11 recognized. As indicated in DSM-III-R (p. 139), caffeine use of even as little as 250 mg/day can cause restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal disturbance, muscle twitching, rambling flow of thought or speech, tachycardia or cardiac arrhythmia, periods of inex- haustibility, and psychomotor agitation. Clinical Criteria Clinical indications for drug abuse include use despite problems from a drug, hazardous use, and unsanc- tioned (i.e., socially disapproved) use (10, 12:. Use despite problems. Case reports describe sub- stance abusers (65) and anorexic patients ; 66) who have persistent, very high caffeine intakes u-ith resul- 36 tant symptoms of intoxication. In some cultures, caf- feine capsules are abused and have been linked to psy- choses and anxiety disorders (67). On the other hand, whether patients persist in the use of caffeine despite physicians' recommendations has not been reported. Hazardous use. Since caffeine intoxication can pro- duce restlessness, excitement, muscle twitches, ram- bling flow of thought, and psychomotor agitation, it is possible that these consequences could impair driving, working with machinery, etc. However, case reports of such events have not been published. Unsanctioned use. A urine screen survey found very high blood levels of caffeine (more than 12.5 mg/ml) in 5% of competitive bicyclists (68). A study of cocaine sam- ples found that caffeine was a common adulterant (69). Summary of Caffeine Abuse Study Results Caffeine can produce positive mood and ampheta- mine-like effects, but these appear to be less robust than those associated with protorypic drugs of abuse. Case reports indicate instances of repeated caffeine intoxica- tion; however, the prevalence of such phenomena is un- clear. Persistent use of caffeine in the face of a known illness aggravated by caffeine has not been documented, nor have caffeine-induced accidents been documented. CAFFEINE DEPENDENCE Basic Science Criteria Demonstration that a drug serves as a reinforcer is thought to be crucial to definitions of drug dependence (70). Reinforcing effects are inferred when subjects con- sistently self-administer a drug at a rate greater than or in preference to placebo. In nonhuman subjects-even those previously trained to self-administer opioids, cocaine, etc.-caffeine either does not serve as a reinforcer or does so marginally or inconsistently (71). Two early studies (72, 73) sug- gested that in humans, caffeine in coffee can serve as a reinforcer, but these studies lacked adequate controls (i.e., decaffeinated coffee or return-to-baseline condi- tions). A third study (60) used preference for ingesting caffeine capsules over placebo capsules to infer rein- forcing effects among light users of caffeine and found no preference for 100-mg or 300-mg caffeinated cap- sules. A fourth study (74) compared the rate of self-ad- ministration of decaffeinated coffee to that of coffee with 25, 50, 100, 200, and 400 mg of caffeine added and found slight increases in administration of the 50- mg and 100-mg doses. In three well-controlled studies by Griffiths et al. (22, 45, 75), a subset of subjects consistently self-administered caffeinated coffee or capsules rather than placebo during double-blind tests. Four studies by our group (24, 76-78) replicated these effects and extended them to low doses (25-50 mg). In several of these studies, caffeine self-ad- ministration was maintained under double-blind condi- Am J Psychiatry 149:1, January 1992

I I I I I I I I I I I I I I I I I 1 I tions across many independent tests (e.g., 12-26 tests) for long periods of time (e.g., 6 months). Although these re- sults were quite robust in some individuals, reasons for individual differences in reinforcing effects have not been established (45, 76, 77). The magnitude of reinforcing effects from caffeine can be estimated by noting how hard human beings will work to obtain caffeine. In one studv (i5 i, the amount of work required in order to obtain cafieinated coffee, decaf- feinated coffee, caffeine capsules. or placebo capsules was increased over time. Self-admirustration of placebo cap- sules dropped off quickly, self-administration of caf- feinated coffee persisted the longest, and decaffeinated coffee and caffeine capsules were self-administered at an intermediate level. In another studv (79), increasing the amount of work required to obtain coffee decreased coffee consumption to an extent similar to that obtained with cigarettes. In that study, subjects made up to 2,500 lever pulls for 2-oz servings of caffeinated coffee. Clinical Criteria The DSM-III-R and ICD-10 dependence criteria of with- drawal symptoms, tolerance. use to avoid withdrawal symptoms, use despite knowledge of harm, and hazard- ous use have alreadv been discussed. We now discuss the five other clinical criteria in DSM-III-R or ICD-10. Loss of control. Tliis criterion is operationalized in DSM-III-R as "substance often taken in larger amounts or over a longer period than the person intended" (p. 167) or "persistent desire or one or more unsuccessful efforts to cut down or control substance use" (p. 168). There are no reports of whether some caffeine users would describe themselves as losing control of their caf- feine intake. Some case reports and clinical reviews sug- gest that there are some patients who wish to quit caf- feine but are unable to do so and that relapse rates are high (44, 80). However, neither prospective studies of attempts to stop using caffeine nor survey data on the prevalence of attempts to stop using caffeine and their success rates are available. '-Nor are there any data on the difficulty that caffeinated coffee users have with switching to decaffeinated coffee. Time with drug. This criterion is defined in DSM-III-R as "a great deal of rime spent in activities necessary to get the substance . . . , taking the substance ..., or re- covering from its effects" (p. 168). Application of this criterion to readily available licit drugs is problematic. Although caffeinated beverages can be quickly made, in some historical periods and in some present cultures, preparation and consumorion of coffeeltea have been described as time-consuming ( 8). To our knowledge, in- stances of spending a great deal of time on preparation and use of beverages containing caffeine have not been reported in the recent Western literature. Progressive neglect. This criterion is defined in DSM- III-R as "important social, occupational, or recrea- tional activities given up or reduced because of sub- stance use" (p. 168). Again, this criterion is not readily applicable, as caffeine is widely available, can be used A}n T Psvchiatrv 149:1. Tanuan., 1992 HUGHES, OL5'ETO, HELZER, ET AL. in social situations, and produces no aftereffects. In- stances of progressive neglect due to caffeine use have not been reported. Narrowing of the repertoire. This criterion is defined in a draft of ICD-10 as "a narrowing of the personal repertoire of patterns of use." The construct is not in- cluded in DSM-1I1-R. Caffeine users do appear to have very regular patterns of use (74); however, the narrow- ing-of-repertoire criterion implies resistance to changes in the pattern of drug intake. Although this has not been tested, most coffee drinkers appear to be flexible with respect to environmentally induced changes in the tim- ing of their caffeine intake, perhaps because caffeine is available in almost all senings. Rapid reinstatement. Rapid reinstatement is defined in the ICD-10 draft as "evidence that return to use after a period of abstinence leads to more rapid reinstate- ment of other features of the syndrome than occurs with nondependent individuals." This construct is also not included in DSM-111-R. At present there are no studies of cessation of caffeine and relapse back to caf- feine use; thus, no data on this construct are available. Construct Validity o f the Dependence Syndrome One important indication of the validity of a disorder is the presence of familial patterns or biological mark- ers. Several studies (81-86) have noted higher concor- dance rates of coffee use among monozygotic twins than among dizygotic twins. Heritabilit,v coefficients were quite similar across most studies: 0.46-0.49. It is important to note that these studies examined coffee use-not abuse, dependence, or withdrawal. Thus, a genetic propensity to use caffeine has been suggested, not a propensity to become dependent. Other studies have noted a higher concordance among monozygotic twins for tolerance to sleep disrup- tion from coffee (87). Another piece of genetic evidence is that taste sensitivity to caffeine is under strong con- trol of genotype (88). Finally, although this is not direct evidence, variations in metabolism of caffeine across users and nonusers occur (89), and persons with faster clearance appear to be more tolerant to the sleep dis- ruption from coffee (90). However, an earlier study did not find this (39). Summary o f Ca f feine Dependence Study Results -4lthough caffeine has not been shown to be a reliable reinforcer in nonhuman subjects, in human beings caf- feine serves as a very reliable reinforcer for some individu- als. Analyses of the strength of caffeine's reinforcing ef- .fects have just begun; thus, it is not possible to conclude whether, in some individuals, caffeine is as strong a rein- forcer as nicotine, alcohol, etc. As indicated earlier, the evidence for withdrawal symptoms and for behavioral harm from caffeine is robust. The evidence for tolerance and physical harm is suggestive. In contrast to these posi- tive results from basic science studies, clinical data on traditional indicators of dependence are clearly lacking. 37

i I I I I I I I I I I I I I I I I I C.kFFEItiE D?SORDERS AND DSA4-/t' CAFFEINE ABLrSE A.tiD DEPE_',-Di<\CE Conclusions With Respect to Caffeine Abuse and Dependence At the present time there is insufficient evidence to include caffeine abuse or dependence in DSM-I1'. This conclusion is based mainlv on the notion that a new disorder should not be included in DSM or ICD until there is a substantial and compelling database. This is especially important with disorders that could be ap- plied to large numbers of individuals. At present a substantial basic research database exists for caffeine dependence (i.e., caffeine can serve as a reinforcer, pro- duce withdrawal, and cause behavioral harm), but a clinical database is almost completely absent. The type of clinical data that would be necessary for adding caf- feine dependence include empirical evidence that a sub- stantial proportion of coffee drinkers 1) try to stop and cannot, 2) have difficulry switching to decaffeinated coffee, and 3) use caffeine despite knowledge that they have health problems which are aggravated by caffeine. Other data of interest would be 4) heavy coffee drink- ers' ratings of the difficulty of stopping caffeine intake compared to stopping cigarette smoking or drinking al- cohol, 5) whether tolerance to important behavioral ef- fects (e.g., relief of fatigue) occurs, 6) whether coffee use escalates over time, 7) how often coffee is used to avoid withdrawal symptoms, and 8) what the prevalence of caffeine dependence is. Exclusion o f Ca f feine Abuse and Dependence and the Goals of DSM Clinical usefulness for making treatment and man- agement decisions. Although we have not recom- mended the inclusion of the diagnoses of caffeine abuse and dependence, some persons might state that their inclusion is needed in order to be consistent Aith the recent emphasis in medical "wellness" and drug-free al- cohoUsubstance abuse programs on complete absti- nence from all drugs. In addition, there is some evidence that caffeine use promotes alcohol use and abuse (8, 47, 91). In a similar vein, inclusion would be consistent with treatment programs that emphasize organismic rather than drug factors in the genesis and maintenance of al- cohoUdrug abuse. In addition, caffeine intake is quite high in some subcultures (8); thus, caffeine dependence might actually be relevant in these settings. Finally, and perhaps most importantly, one could argue that inclu- sion of caffeine abuse would promote identificarion of patients who repeatedly experience intoxication and would suggest that in addition to treatment for caffeine intoxication, such patients need acute treatment for an abuse/dependence problem. On the other hand, one clinical reason not to include caffeine abuse and dependence is that caffeine intoxica- tion is already included in DSM-II7-R and that such a diagnosis should remind psychiatrists that excessive caffeine use can mimic several psychiatric conditions, including anxietv disorders and drug withdrawal. A second clinical reason for not including caffeine abuse and dependence is that, at present, only a few treat- merits for caffeine abuse and dependence have been tested (92, 93). Whether treatments used for other drugs (e.g., 12-step programs, behavioral therapy, pharmacological replacement) would be efficacious is debatable. Thus, the therapeutic benefits of a diagnosis of caffeine abuse or dependence are nor clear. Finally, at present patients with symptoms of caffeine dependence can be given the DSM-III-R diagnosis of psy- choactive substance dependence not other-wise specified. This residual category is for disorders that occur infre- quently. Thus, a determination of the prevalence of caf- feine dependence phenomena both in treatment settings and in the general population would be helpful in deciding whether a new disorder should be created or whether in- stances of caffeine dependence are so infrequent that they should continue to be put in this residual category. Acceptability to clinicians and researchers. A decision to exclude caffeine abuse and dependence could pro- voke negative comments from primary care physicians, psychiatrists, and substance abuse clinicians who have patients who recognize that caffeine is aggravating their disorders, who have severe headaches upon cessation of caffeine, or who are unable to stop caffeine use. Such clinicians might accuse DSM-1V of being inconsistent in its handling of various drug use problems or of being politically cowardly. A decision to include caffeine abuse and dependence may provoke negative comments from coffee manufac- rurers, the general public, and some substance abuse clinicians. Coffee manufacturers will obviously fear a public debate like that which occurred with respect to tobacco. The general public and some substance abuse clinicians will state that inclusion of caffeine depend- ence trivializes other more damaging substance use disorders, promotes the view of DSM as a tool for psychiatrists to aggrandize diagnostic territory, and un- dermines the credibility of APA. These groups will fo- cus on the lack of clinical information on caffeine abuse and dependence and the absence of studies comparing the relative strengths of caffeine dependency versus al- cohol, nicotine, and other dependencies. FINAL COMMENT Whether caffeine withdrawal, caffeine abuse, or caf- feine dependence should be added to the DSM or ICD- 10 classifications will be a controversial topic. This ar- ticle was written in the belief that empirical data and established criteria for acceptance of disorders are bet- ter guides for such a decision than a priori beliefs or philosophical positions. REFERENCES 1. 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